This Phase II SBIR program aims to further develop Electronic Bio Sciences'(EBS) Nanopatch system for ion channel measurements. The proposed system will allow high sensitivity measurements previously only attainable with the patch clamp method to be performed on a planar lipid bilayer (PLB) system. The system relies on a nanometer scale bilayer on the quartz nanopore membrane platform and EBS designed electronics to reduce the noise typically associated with a traditional PLB system. The aims of this program are to improve the low frequency noise performance to rival that of patch clamping, adapt established protocols and develop new methods to increase the types of ion channels that can be incorporated into the Nanopatch system and demonstrate the capabilities of the system using an intracellular channel with low conductance and fast kinetics. Four prototype Nanopatch systems will also be produced. This improved Nanopatch system will have several distinct advantages over currently available ion channel measurement apparatus including a low noise, high bandwidth platform, robust and reproducible bilayer formation, fine temperature and pressure control and automated bilayer formation and ion channel incorporation. The proposed Nanopatch system will enable a large range of low conductance channels and channels with fast kinetics to be evaluated in a PLB at previously unattainable resolution and sensitivity. PUBLIC HEALTH RELEVANCE: Ion channels are critical in an enormous range of physiological functions ranging from control of nerve impulses to cardiac regulation and medical researchers are discovering tens to hundreds of new channelopathies per year as many diseases are being recognized that arise from channel malfunction. In order to exploit this knowledge for new drugs targeting these channels, a complete characterization of the individual channel conductance is needed. The Nanopatch system will provide a means to achieve this characterization as well as increase the number of channels that can be investigated, substantially decrease the difficulty in obtaining these measurements and allow complete dose effect curves to be obtained due to increased measurement times with the robust bilayer platform.